Can TILs Help to Determine Outcomes in Triple-Negative Breast Cancer?

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High levels of tumor-infiltrating lymphocytes (TILs) within the tumors of patients with early-stage triple-negative breast cancer may be associated with a lower risk of cancer recurrence and greater rate of survival, even without chemotherapy, according to a recent study published by Leon-Ferre et al in JAMA.


Triple-negative breast cancer—a breast cancer subtype that does not respond to estrogen receptor– or HER2-targeted therapy—is known to grow rapidly and may be more likely to spread beyond the breast prior to diagnosis and recur compared with other breast cancer subtypes. Triple-negative breast cancer represents about 15% of all breast cancer cases and is most prevalent among younger, female patients who identify as Black, Hispanic, and Indian.

Most patients with early-stage triple-negative breast cancer undergo chemotherapy either prior to or following surgery—including those with stage I breast cancer—and receive a combination of multiple chemotherapy drugs, which can cause significant side effects. Currently, the main factors taken into consideration when determining the course of chemotherapy are the tumor size and presence of lymph node metastases. However, the number of TILs further influences the risk of future cancer recurrence. These naturally occurring immune system cells, which can travel from the bloodstream into a tumor, are capable of recognizing and destroying cancer cells.

“TILs are not currently measured or reported in the routine examination of tissue samples of breast cancer,” explained co–senior study author Matthew Goetz, MD, the Erivan K. Haub Family Professor of Cancer Research Honoring Richard F. Emslander, MD, and a medical oncologist at the Mayo Clinic Comprehensive Cancer Center. “While prior studies have focused on measuring TILs in [patients] treated with chemotherapy, this is the largest study to comprehensively demonstrate that the presence of TILs influences the natural behavior of breast cancer in [patients] who have surgery and/or radiation with no additional medical treatment,” he added.

“[T]he first report suggesting that an increased number of immune cells [was] associated with better prognosis in patients [with breast cancer] was described by [physicians] at [the] Mayo Clinic more than 100 years ago. It took a global effort and a century later to reexamine this biomarker and bring it closer to application in patient care,” noted co–lead study author Roberto Salgado, MD, PhD, Co-Chair of the International Immuno-Oncology Biomarker Working Group. “The results of this study could lead to a recommendation to include TILs in the pathology reports of early-stage [triple-negative breast cancer] worldwide, as it has the potential to inform clinicians and patients when they discuss treatment options,” he continued.

Study Methods and Results

In the recent multicenter, international study, researchers analyzed the outcomes of 1,966 patients with early-stage triple-negative breast cancer who underwent surgery with or without radiation therapy but did not receive chemotherapy. After a median follow-up of 18 years, the researchers discovered that the patients with higher levels of TILs in their breast cancer tissue were less likely to experience cancer recurrence.

“Five years after surgery, 95% of participants with small tumors, stage I [triple-negative breast cancer], and whose tumors had high [levels of] TILs were alive, compared [with] 82% of patients whose tumors had low TILs. Importantly, the breast cancer recurrence rate was significantly lower among patients whose tumors had high TILs,” emphasized co–senior study author Stefan Michiels, PhD, Head of the Oncostat team at Gustave Roussy, Inserm U1018, and the University Paris-Saclay. “With nearly 2,000 participants involved in the study, we have now assembled the largest international cohort across three continents of [patients] with [triple-negative breast cancer] in which the primary treatment was surgery without chemotherapy,” he highlighted.

Further, the researchers found that this biomarker would only require a visual evaluation by a pathologist, meaning there may be no additional costs associated with identifying the presence of TILs. The strategy could be particularly beneficial in regions with limited resources.


“This is an important finding because it highlights that the abundance of TILs in breast tissue is a prognostic biomarker in [patients] with early-stage triple-negative breast cancer, even when chemotherapy is not administered. The study’s findings may inspire future clinical trials to explore whether patients with a favorable prognosis (high TILs) can avoid intensive chemotherapy regimens,” underscored co–lead study author Roberto Leon-Ferre, MD, a breast medical oncologist at the Mayo Clinic Comprehensive Cancer Center.

“This meta-analysis confirms robustly the prognostic value of TILs that we have previously reported in patients [with triple-negative breast cancer] treated with chemotherapy and expands it to patients treated without chemotherapy. Future studies may allow the use of this biomarker along with standard clinicopathological factors to inform treatment decisions in patients [with triple-negative breast cancer],” proposed co–lead study author Sarah Flora Jonas, PhD, a statistician at Gustave Roussy.

The researchers plan to further explore TILs as biomarkers in prospective clinical trials evaluating chemotherapy selection based on patients’ TIL levels. Ongoing efforts to conduct additional research with other potential biomarkers are underway.

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